B2O3/Al2O3 as a new, highly efficient and reusable heterogeneous ...

Article

J. Braz. Chem. Soc., Vol. 21, No. 8, 1552-1556, 2010. Printed in Brazil - ©2010 Sociedade Brasileira de Química 0103 - 5053 $6.00+0.00

B2O3/Al2O3 as a New, Highly Efficient and Reusable Heterogeneous Catalyst for the Selective Synthesis of β-Enamino Ketones and Esters under Solvent-Free Conditions Jiu-Xi Chen,a Chang-Fu Zhang,b Wen-Xia Gao,a Hui-Le Jin,a Jin-Chang Dinga,b and Hua-Yue Wu*,a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325035, China

a

Wenzhou Vocational and Technical College, Wenzhou, 325035, China

b

Óxido de boro adsorvido sobre alumina (B2O3/Al2O3) foi usado como um novo e eficiente catalisador na síntese de β-aminocetonas e ésteres pela enaminação de diferentes aminas primárias e secundárias com compostos carbonílicos sob condições livre de solvente. A importância dessa metodologia congrega grande variedade de substratos, alta eficiência, ausência de catalisador metálico, alta régio- e quimioseletividade em condições amigáveis ao ambiente. Ainda, o catalisador pode ser recuperado facilmente depois das reações e reusado sem perda de atividade. Boron oxide adsorbed on alumina (B2O3/Al2O3) has been found to be a new and highly efficient heterogeneous catalyst for the synthesis of β-enamino ketones and esters by the enamination of various primary and secondary amines with β-dicarbonyl compounds under solvent-free conditions. The important features of this methodology are broad substrate scope, high yield, no requirement of metal catalysts, high regio- and chemoselectivity and environmental friendliness. In addition, the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity. Keywords: β-enamino ketones, β-enamino esters, β-dicarbonyl compounds, amines, B2O3/Al2O3, solvent-free

Introduction β-Enamino carbonylic compounds represent an important class of functionalized building blocks, which become increasingly important in medicinal chemistry and organic synthesis.1 Consequently, various approaches toward the construction of β-enamino carbonylic compounds have been explored during the past years. The direct enamination of 1,3-dicarbonyl compounds with amines is one of the most straightforward methods for the synthesis of β-enamino ketones and esters in the presence of various promoting agents.2-19 Recent reports have described the preparation of β-enamino ketones and esters catalyzed by metal triflate.20 Although the reported methodologies are suitable for certain synthetic conditions, some of these procedures suffered from disadvantages, such as long reaction time, low yield, use of volatile organic solvents, requirement of excess of reagents or costly catalysts, special apparatus and harsh reaction conditions. Therefore, the development *e-mail: [email protected]

of convenient, environmental friendliness, high yield and clean approaches is highly desirable. Recently, heterogeneous organic reactions21 have been recently performed with immobilized reagents on solid supports. These procedures offer several intrinsic advantages such as clean reactions, the easy separation of products, the recover and reuse of catalyst conveniently, the minimization of waste production, and eco-friendliness etc. As a part of our great interest in developing novel synthetic routes for the formations of carbon-carbon and carbon-heteroatom bonds,22 we herein reported B2O3/Al2O3 as a new, efficient and reusable heterogeneous catalyst for the enamination of β-dicarbonyl compounds with amines.

Results and Discussion The model reaction of ethyl acetoacetate (1a) with aniline (2a) was conducted to find the optimal reaction conditions and the initial results are listed in Table 1. First, the effect of solvents was tested. Among all the solvents tested, ethanol afforded better yield than some other solvents tested. As shown in Table 1, however,

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Chen et al.

Table 1. The condensation of ethyl acetoacetate with aniline under various different reaction conditionsa

O

O OEt

+ PhNH2

1a Entry

B2O3/Al2O3 r.t.

Ph

2a

NH

O 3a

OEt

Solvent

time (h)

Yields (%)b

1

EtOH

1

75

2

CH3CN

1

68

3

CH2Cl2

1

70

4

H2O

1

65

5

none

1

95

6

none

2.5

96

7

none

1

85c

8

none

1

95 (22)e

9

none

5

40f

d

All reactions were run with 1a (1 mmol), 2a (1.1 mmol) and B2O3/Al2O3 (0.03 g, 15% m/m) in 2 mL of solvent at room temperature. bIsolated yields. B2O3/Al2O3 (0.01 g, 15% m/m) was used as a catalyst. dB2O3/Al2O3 (0.05 g, 15% m/m) was used as a catalyst. eIn the absence of catalyst. f Al2O3 (0.03 g) was used as a catalyst. a c

the presence of additional solvents lowered the reaction rate (Table 1, entries 1-4). So we chose to perform this reaction under solvent-free conditions (Table 1, entry 5). In contrast, the product 3a was obtained in 22% yield in the absence of B2O3/Al2O3 (Table 1, entry 8). When only Al2O3 was used as a catalyst, 3a was obtained in 40% yield (Table 1, entry 9). On the other hand, it was found that the yield was affected by adding different amount of B2O3/Al2O3 (Table 1, entries 5, 7-8). Thus, subsequent studies were carried out under the following optimized conditions, that are, 0.03 g B2O3/Al2O3 at room temperature in the absence of solvent. With optimal conditions in hand, the reaction of different β-dicarbonyl compounds 1 with a range of primary, secondary, and aromatic amines 2 were examined to explore the scope of the reaction. As shown in Table 2, a series of aromatic amines bearing either electron-donating or electron-withdrawing groups on aromatic ring were investigated. The substituent groups on the aromatic ring associated with amines did not show obvious effects in terms of yields under optimal conditions. It was observed that the corresponding β-enamino ketones and esters 3 were obtained in good to excellent yields. Aliphatic amines also reacted efficiently to give products 3m-3p in good yields, and the reaction time was shorter than that of aromatic amines (Table 2, entries 13-16). Moreover, secondary amines reacted to afford products 3q3s in good yields but with longer reaction times (Table 2, entries 17-19). Next, we investigated the reaction of β-dicarbonyl compounds 1 with diamines 4 (Table 3). In this reaction, two

equivalents of 1 were required in order to have a complete conversion of diamines. When aliphatic diamine such as 1,3-propanediamine was examined, the corresponding bisenamine products 5a and 5b were obtained in 95 and 99% yields, respectively. Moreover, when aromatic diamine such as 1,4-benzenediamine was examined, the corresponding bis-enamine products 5c and 5d were obtained in 88 and 97% yields, respectively. However, when more sterically hindered aromatic diamine such as 1,2-benzenediamine was examined, the reaction only gave the mono-enamine products 6a and 6b using two equivalents and even three equivalents of β-dicarbonyl compounds. On the other hand, we have investigated the efficiency of this catalyst for a few representative intermolecular competition studies (Scheme 1). The different reactivity of aromatic amines and aliphatic amines were demonstrated during the reaction of β-dicarbonyl compounds such as ethyl acetoacetate and acetylacetone with equimolar mixtures of aniline and n-propylamine (selectivity in favour of n-propylamine). Analysis of the mixture after 2 h showed that only n-propylamine reacted with ethyl acetoacetate and acetylacetone. Finally, the reusability of B2O3/Al2O3 was further investigated in subsequent reactions, taking the additions of aniline to ethyl acetoacetate as an example (Scheme 2). The catalyst was easily recovered by simple filtration after diluting of the reaction mixture with ethyl acetate and was reused after being dried under vacuum. B2O3/Al2O3 was reused for four runs without evident loss of activity.

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B2O3/Al2O3 as a New, Highly Efficient and Reusable Heterogeneous Catalyst

J. Braz. Chem. Soc.

Table 2. Synthesis of β-enamino carbonylic compounds catalyzed by B2O3/Al2O3a

O

O +

R1

R2

H N

1 Entry 1

R2

B2O3/Al2O3 R3

N

R3

O

r.t.

R1

2

3

R1

R2

R3

time

Product

Yield (%)b

OEt

Ph

H

1h

3a

95

2

Me

Ph

H

2h

3b

87

3

OEt

α-naphtyl

H

3h

3c

86

4

Me

α-naphtyl

H

4h

3d

90

5

OEt

4-CH3C6H4

H

1.5 h

3e

88

6

Me

4-CH3C6H4

H

1.5 h

3f

86

7

OEt

2-CH3OC6H4

H

2h

3g

85

8

Me

2-CH3OC6H4

H

2h

3h

89

9

OEt

3-ClC6H4

H

2h

3i

83

10

Me

3-ClC6H4

H

2h

3j

71 (98)c

11

OEt

4-ClC6H4

H

1.5 h

3k

78 (91)c

12

OEt

4-BrC6H4

H

2h

3l

73 (86)c

13

OEt

CH3CH2CH2

H

20 min

3m

91

14

Me

CH3CH2CH2

H

20 min

3n

88

15

OEt

PhCH2

H

50 min

3o

80

16

Me

PhCH2

H

50 min

3p

86

17

Me

CH3CH2

CH3CH2

5h

3q

83

18

Me

morpholine

5h

3r

83

19

OEt

morpholine

5h

3s

82

All reactions were run with 1 (1 mmol), 2 (1.1 mmol) and B2O3/Al2O3 (0.03 g, 15% m/m) in the absence of solvent at room temperature. b Isolated yields. c 50 oC. a

O PhNH2 O

O R1

Ph R1 = OEt, 3a

R1

NH2

R1 = Me, 3b

0%

B2O3/Al2O3 r.t.

+

HN

O

HN

n

Pr

R1 = OEt, 3m R1 = Me, 3n

R1 100%

Scheme 1. Chemoselective reaction.

O

O OEt

+ PhNH2

O

B2O3/Al2O3 r.t.

EtO

Run 1: 95%; Run 2: 95%; Run 3: 92%; Run 4: 91% Scheme 2. Reuse of the catalyst.

HN 3a

Ph

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Chen et al.

Table 3. Reaction of β-dicarbonyl compounds with diamines catalyzed by B2O3/Al2O3a

O

O R1

+ H2N

R2

1 Entry

1

N H

B2O3/Al2O3 r.t.

R1

O

Diamine 4

H2N

N H

Me

H2N

NH2

R2

+

6 Product

O

20 min

HN

Yield (%)b

NH

O

95

OEt 5a O

5 min

NH2

1 R1 R

EtO 2

HN

5 time

NH2

O O

4

R1

OEt

NH2

R2

HN

NH

O

99 5b

O

O 3

OEt

H2N

NH2

1h

OEt

NH

HN

EtO

88 5c

O

O 4

Me

H2N

NH2

1h

NH

HN

97 5d

H2N

NH2 5

OEt

4h

NH2

O EtO

Me

6a

H2N

NH2 6

86

HN

3.5 h

NH2

O

81

HN 6b

a

All reactions were run with 1 (2 mmol), 4 (1 mmol) and B2O3/Al2O3 (0.03 g, 15% m/m) in the absence of solvent at room temperature. b Isolated yields.

Conclusions In conclusion, we have reported B2O3/Al2O3 as a highly efficient heterogeneous reusable catalyst for chemoselective enamination of β-dicarbonyl compounds with aliphatic and aromatic amines under solvent-free conditions. In addition, the important features of this procedure are mild reaction conditions, high yield, and operational simplicity which make it a useful and attractive strategy for the preparation of N-substituted β-enamino carbonylic compounds.

Experimental Melting points were recorded on Digital Melting Point Apparatus WRS-1B and were uncorrected. 1H NMR

and 13C NMR spectra were taken on a Bruker DPX300 spectrometer using CDCl 3 as the solvent with tetramethylsilane (TMS) as an internal standard at room temperature. Chemical shifts were given in δ relative to TMS, the coupling constants J are given in Hz. General procedure for the preparation of b-enamino ketones and esters To a magnetically stirred mixture of the β-dicarbonyl compounds (1 mmol) and amines (1.1 mmol), B2O3/Al2O3 (0.03 g, 15% m/m) was added and the reaction mixture was stirred at room temperature for the appropriate time. The reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with ethyl


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J. Braz. Chem. Soc.

acetate. The catalyst was separated by filtration, then the solution was washed with ethyl acetate (5 mL) and dried over anhydrous sodium sulfate, filtered and the solvent was evaporated under vacuum. The residue was purified by flash column chromatography to afford the desired product. The spectral and analytical data of all compounds are given in Supporting Information.

8. Ceric ammonium nitrate: Duan, Z.; Li, T.; Xuan, X. J.; Wu, Y.

Supplementary Information

11. ZrOCl2·8H2O: Zhang, Z. H.; Li, T. S.; Li, J. J.; Catal. Commun.

J.; Chin. Chem. Lett. 2006, 17, 1566; Sridharan, V.; Avendano, C.; Menendez, J. C.; Synlett 2007, 881; Mo, L. P.; Liu, S. F.; Li, W. Z.; J. Chin. Chem. Soc. 2007, 54, 879. 9. 12-Tungstophosphoric acid: Chen, X.; She, J.; Shang, Z. C.; Wu, J.; Wu, H. F.; Zhang, P. Z.; Synthesis 2008, 3478. 10. InBr3: Zhang, Z. H.; Yin, L.; Wang, Y. M.; Adv. Synth. Catal. 2006, 348, 184 and references cited therein. 2007, 8, 1615.

Supplementary data are available free of charge at http://jbcs.sbq.org.br, as PDF file.

Acknowledgments

12. CoCl2: Zhang, Z. H.; Hu, J. Y.; J. Braz. Chem. Soc. 2006, 17, 1447. 13. Silica-supported sulfuric acid: Chen, X.; She, J.; Shang, Z. C.; Wu, J.; Zhang, P. Z.; Synth. Commun. 2009, 39, 947. 14. Silica-supported antimony(III) chloride: Zhang, L. F.; Yang, S.

We are grateful to the National Key Technology R&D Program (No. 2007BAI34B00) and the Natural Science Foundation of Zhejiang Province (No. Y4080107) for financial support.

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Chem. Soc. 1990, 112, 3483; Aceña, J. L.; Arjona, O.; Mañas, R.; Plumet, J.; J. Org. Chem. 2000, 65, 2580. 2. Microwave: Rechsteimer, B.; Texier-Boullet, F.; Hamelin, J.; Tetrahedron Lett. 1993, 34, 5071. 3. Ultrasound: Valduga, C. J.; Squizani, A.; Braibante, H. S.; Braibante, M. E. F.; Synthesis 1998, 1019; Brandt, C. A.; da Silva, A. C. M. P.; Pancote, C. G.; Brito, C. L.; da Silveira, M. A. B.; Synthesis 2004, 1157. 4. NaAuCl4: Arcadi, A.; Bianchi, G.; Giuseppe, S. D; Marinelli, F.; Green Chem. 2003, 5, 64. 5. Zn(ClO4)2: Bartoli, G.; Bosco, M.; Locatelli, M.; Marcantoni, E.; Melchiorre, P.; Sambri, L.; Synlett 2004, 239. 6. Bi(TFA)3: Khosropour, A. R.; Khodaei, M. M.; Kookhazadeh, M.; Tetrahedron Lett. 2004, 45, 1725.

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Received: December 1. 2009 Web Release Date: April 27, 2010

J. Braz. Chem. Soc., Vol. 21, No. 8, S1-S28, 2010. Printed in Brazil - ©2010 Sociedade Brasileira de Química 0103 - 5053 $6.00+0.00

Jiu-Xi Chen,a Chang-Fu Zhang,b Wen-Xia Gao,a Hui-Le Jin,a Jin-Chang Dinga,b and Hua-Yue Wu*,a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325035, China

a

Wenzhou Vocational and Technical College, Wenzhou, 325035, China

b

Description of the products (Z)-Ethyl 3-(phenylamino)but-2-enoate (3a)1 Oil, IR (KBr) nmax/cm-1: 3456, 3258, 2979, 1610, 1495, 1442, 1370, 1270, 1162, 1056 cm–1. 1H NMR (300 MHz, CDCl3): d 10.41 (br s, 1H, NH), 7.30-7.35 (m, 2H), 7.08-7.18 (m, 3H), 4.71 (s, 1H), 4.17 (q, J 7.2 Hz, 2H), 2.01 (s, 3H), 1.32 (t, J 7.2 Hz, 3H). 13C MNR (75 MHz, CDCl3): d 170.4, 158.9, 139.3, 129.0, 124.9, 124.4, 85.9, 58.7, 20.3, 14.6. (Z)-4-(Phenylamino)pent-3-en-2-one (3b) Solid, mp: 47-49 oC (Lit.1 48-49 oC); IR (KBr) nmax/cm-1: 3349, 2980, 1605, 1499, 1432, 1276, 1183, 1017, 746; 1H NMR (300MHz, CDCl3): d 12.46 (br s, 1H, NH), 7.25-7.30 (m, 2H), 7.03-7.15 (m, 3H), 5.14 (s, 1H), 2.05 (s, 3H), 1.93 (s, 3H); 13C MNR (75MHz, CDCl3): d 196.0, 160.2, 138.6, 129.0, 125.5, 124.6, 97.6, 29.1, 19.8. (Z)-Ethyl 3-(naphthalen-1-ylamino)but-2-enoate (3c)2 Oil; IR (KBr) nmax/cm-1:: 3246, 3056, 2978, 1605, 1441, 1384, 1266, 1165, 785; 1H NMR (300MHz, CDCl3): d 10.61 (br s, 1H, NH), 8.06-8.09 (m, 1H), 7.86-7.89 (m, 1H), 7.75 (d, J 8.4 Hz, 1H), 7.26-7.57 (m, 4H), 4.83 (s, 1H), 4.23 (q, J 7.2Hz, 2H), 1.86 (s, 3H), 1.34 (q, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.7, 160.5, 135.3, 134.3, 130.4, 128.2, 126.7, 126.5, 126.4, 125.3, 123.6, 122.7, 85.7, 58.8, 20.04, 14.7. (Z)-4-(Naphthalen-1-ylamino)pent-3-en-2-one (3d) Solid, mp: 61-63 oC (Lit.3 51-53 oC); IR (KBr) nmax/ cm-1: 3430, 2972, 1600, 1550, 1425, 1278, 1078, 1015, 774; 1H NMR (300MHz, CDCl3): d 12.76 (br s, 1H, NH), 8.02-8.05 (m, 1H), 7.87-7.90 (m, 1H), 7.77 (d, J 8.4Hz, 1H), 7.27-7.56 (m, 4H), 5.32 (s, 1H), 2.18 (s, 3H), 1.88 (s, 3H); 13C MNR (75MHz, CDCl3): d 196.6, 161.9, 134.8, *e-mail: [email protected]

134.2, 123.0, 128.2, 126.9, 126.9, 126.5, 125.5, 123.4, 122.8, 97.4, 29.2, 19.6. (Z)-Ethyl 3-(p-toluidino)but-2-enoate (3e)1 Oil; IR (KBr) nmax/cm-1: 3257, 3189, 2979, 1615, 1509, 1441, 1271, 1161, 1059, 792; 1H NMR (300MHz, CDCl3): d 10.28 (br s, 1H, NH), 7.10-7.13 (m, 2H), 6.96-6.99 (m, 2H), 4.66 (s, 1H), 4.14 (q, J 7.2Hz, 2H), 2.33 (s, 3H), 1.95 (s, 3H), 1.28 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.5, 158.8, 136.7, 134.9, 129.6, 124.7, 85.3, 58.7, 20.9, 20.3, 14.6. (Z)-4-(p-Toluidino)pent-3-en-2-one (3f) Solid, mp: 66-67 oC (Lit.4 68-69 oC); IR (KBr) nmax/cm‑1: 3448, 2922, 1607, 1508, 1434, 1276, 1178, 1013, 822, 753; 1H NMR (300MHz, CDCl3): d 12.40 (br s, 1H, NH), 7.14 (d, J 8.4Hz, 2H), 7.00 (d, J 8.4Hz, 2H), 5.16 (s, 1H), 2.34 (s, 3H), 2.09 (s, 3H), 1.96 (s, 3H); 13C MNR (75MHz, CDCl3): d 195.9, 160.7, 136.1, 135.5, 129.6, 124.8, 97.2, 29.1, 20.9, 19.7. (Z)-Ethyl 3-(2-methoxyphenylamino)but-2-enoate (3g)5 Oil; IR (KBr) nmax/cm-1: 3262, 2976, 1614, 1464, 1376, 1220, 1161, 1037, 746; 1H NMR (300MHz, CDCl3): d 10.28 (br s, 1H, NH), 7.08-7.14 (m, 2H), 6.88-6.92 (m, 2H), 4.71 (s, 1H), 4.16 (q, J 7.2Hz, 2H), 3.86 (s, 3H), 2.01 (s, 3H), 1.28 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.2, 158.9, 152.6, 128.6, 125.3, 124.4, 120.3, 111.0, 86.3, 58.7, 55.7, 20.4, 14.6. (Z)-4-(2-Methoxyphenylamino)pent-3-en-2-one (3h)5 Oil; IR (KBr) nmax/cm-1: 3456, 2949, 2841, 1607, 1481, 1344, 1274, 1180, 1025, 747; 1H NMR (300MHz, CDCl3): d 12.32 (br s, 1H, NH), 7.01-7.18 (m, 2H), 6.87-6.93 (m, 2H), 5.20 (s, 1H), 3.86 (s, 3H), 2.10 (s, 3H), 1.99 (s, 3H); 13 C MNR (75MHz, CDCl3): d 195.9, 160.4, 152.8, 128.0, 126.2, 125.0, 120.3, 111.2, 97.8, 55.7, 29.1, 20.0.

Supplementary Information

B2O3/Al2O3 as a New, Highly Efficient and Reusable Heterogeneous Catalyst for the Selective Synthesis of β-Enamino Ketones and Esters under Solvent-Free Conditions

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(Z)-Ethyl 3-(3-chlorophenylamino)but-2-enoate (3i)6 Oil; IR (KBr) nmax/cm-1: 3190, 2979, 1637, 1476, 1370, 1270, 1164, 1074, 784; 1H NMR (300MHz, CDCl3): d 10.42 (br s, 1H, NH), 7.10-7.22 (m, 3H), 6.94-6.96 (m, 1H), 4.72 (s, 1H), 4.15 (q, J 7.2Hz, 2H), 2.02 (s, 3H), 1.28 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.3, 158.0, 140.7, 134.6, 130.0, 124.7, 123.9, 122.1, 87.5, 59.0, 20.4, 14.6. (Z)-4-(3-Chlorophenylamino)pent-3-en-2-one (3j) Solid, mp: 37-39 oC (Lit.1 39-40 oC); IR (KBr) nmax/cm‑1: 3428, 2978, 1578, 1491, 1429, 1276, 1186, 1020, 937, 772; 1H NMR (300MHz, CDCl3): d 12.47 (br s, 1H, NH), 6.98-7.29 (m, 4H), 5.22 (s, 1H), 2.11 (s, 3H), 2.02 (s, 3H); 13 C MNR (75MHz, CDCl3): d 196.4, 157.8, 140.2, 128.1, 127.5, 124.9, 118.3, 115.7, 97.0, 43.2, 19.3. (Z)-Ethyl 3-(4-chlorophenylamino)but-2-enoate (3k) Solid, mp: 52-54 oC (Lit.1 54-55 oC); IR (KBr) nmax/cm-1: 3457, 2980, 1633, 1491, 1383, 1272, 1160, 787; 1H NMR (300MHz, CDCl3): d 10.34 (br s, 1H, NH), 7.22-7.26 (m, 2H), 6.97-6.99 (m, 2H), 4.69 (s, 1H), 4.12 (q, J 7.2Hz, 2H), 1.95 (s, 3H), 1.26 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.4, 158.3, 138.0, 130.2, 129.2, 125.5, 86.9, 58.9, 20.2, 14.6. (Z)-Ethyl 3-(4-bromophenylamino)but-2-enoate (3l) Solid, mp: 53-55 oC (Lit.3 54-55 oC); IR (KBr) nmax/cm-1: 3451, 3273, 2924, 1622, 1482, 1358, 1269, 1163, 1059, 786; 1H NMR (300MHz, CDCl3): d 10.35 (br s, 1H, NH), 7.38-7.43 (m, 2H), 6.91-6.96 (m, 2H), 4.70 (s, 1H), 4.12 (q, J 7.2Hz, 2H), 1.97 (s, 3H), 1.26 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.3, 158.2, 138.5, 132.1, 125.7, 117.9, 87.0, 58.9, 20.3, 14.6. (Z)-Ethyl 3-(propylamino)but-2-enoate (3m)7 Oil; IR (KBr) nmax/cm-1: 3285, 2965, 1609, 1448, 1270, 1160, 1065, 784, 695; 1H NMR (300MHz, CDCl3): d 8.51 (br s, 1H, NH), 4.36 (s, 1H), 4.00-4.03 (m, 2H), 3.07-3.11 (m, 2H), 1.85 (s, 3H), 1.49-1.53 (m, 2H), 1.16-1.18 (m, 3H), 0.90-0.91 (m, 3H); 13C MNR (75MHz, CDCl3): d 170.5, 161.8, 81.6, 58.0, 44.5, 23.5, 19.2, 14.5, 11.2. (Z)-4-(Propylamino)pent-3-en-2-one (3n)8 Oil; IR (KBr) nmax/cm-1: 3451, 2960, 1603, 1443, 1359, 1295, 740, 647; 1H NMR (300MHz, CDCl3): d 10.85 (br s, 1H, NH), 4.93 (s, 1H), 3.14-3.21 (m, 2H), 1.98 (s, 3H), 1.90 (s, 3H), 1.53-1.62 (m, 2H), 0.93-0.98 (m, 3H); 13C MNR (75MHz, CDCl3): d 194.8, 163.1, 95.0, 44.8, 28.7, 23.3, 18.8, 11.3.

J. Braz. Chem. Soc.

(Z)-Ethyl 3-(benzylamino)but-2-enoate (3o)5 Oil; IR (KBr) nmax/cm-1: 3289, 2977, 1605, 1499, 1445, 1280, 1169, 1113, 786, 697; 1H NMR (300MHz, CDCl3): d 8.96 (br s, 1H, NH), 7.24-7.37 (m, 5H), 4.54 (s, 1H), 4.43 (d, J 6.3Hz, 2H), 4.10 (q, J 7.2Hz, 2H), 1.92 (s, 3H), 1.26 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.5, 161.7, 138.7, 128.7, 127.2, 126.6, 83.1, 58.3, 46.7, 19.3, 14.5. (Z)-4-(Benzylamino)pent-3-en-2-one (3p)5 Oil; IR (KBr) nmax/cm-1: 3446, 2926, 1605, 1509, 1441, 1360, 1295, 1104, 1023, 739; 1H NMR (300MHz, CDCl3): d 11.16 (br s, 1H, NH), 7.24-7.36 (m, 5H), 5.04 (s, 1H), 4.45 (d, J 6.3Hz, 2H), 2.03 (s, 3H) 1.91 (s, 3H); 13C MNR (75MHz, CDCl3): d 195.3, 163.0, 138.0, 128.7, 127.3, 126.6, 95.8, 46.6, 28.8, 18.8. 4-(Diethylamino)pent-3-en-2-one (3q)9 Oil; IR (KBr) nmax/cm-1: 2975, 1628, 1538, 1439, 1355, 1193; 1H NMR (300MHz, CDCl3): d 5.07 (s, 1H), 3.253.32 (m, 4H), 2.51 (s, 3H), 2.05 (s, 3H), 1.13-1.18 (m, 6H); 13C MNR (75MHz, CDCl3): d 194.1, 160.0, 93.8, 43.7, 15.1, 12.4. 4-Morpholinopent-3-en-2-one (3r)1 Oil; IR (KBr) nmax/cm-1: 2964, 2854, 1640, 1544, 1431, 1257, 1184, 1119; 1H NMR (300MHz, CDCl3): d 5.21 (s, 1H), 3.64-3.71 (m, 4H), 3.26-3.30 (m, 4H), 2.43 (s, 3H), 1.97 (s, 3H); 13C MNR (75MHz, CDCl3): d 195.5, 160.6, 96.9, 66.5, 45.8, 30.7, 15.1. Ethyl 3-morpholinobut-2-enoate (3s)9 Oil; IR (KBr) nmax/cm-1: 2970, 2854, 1688, 1584, 1435, 1259, 1144, 998, 805; 1H NMR (300MHz, CDCl3): d 4.78 (s, 1H), 4.06-4.12 (m, 2H), 3.69-3.73 (m, 4H), 3.19-3.23 (m, 4H), 2.40 (s, 3H), 1.22-1.27 (m, 3H); 13C MNR (75MHz, CDCl3): d 168.6, 160.9, 88.1, 66.0, 58.4, 46.1, 15.0, 14.2. (2Z, 2’Z)-Diethyl 3, 3’-(propane-1, 3-diylbis(azanediyl)) dibut-2-enoate (5a)1 Oil; IR (KBr) nmax/cm-1: 3283, 3193, 2977, 2248, 1604, 1270, 913, 787, 726, 554; 1H NMR (300MHz, CDCl3): d 8.47 (br s, 2H, NH), 4.37 (s, 2H), 3.98 (q, J 7.2Hz, 4H), 3.22 (q, J 6.3Hz, 4H), 1.82 (s, 6H), 1.74-1.76 (m, 2H), 1.15 (t, J 7.2Hz, 6H); 13C MNR (75MHz, CDCl3): d 170.5, 161.7, 82.6, 58.2, 39.7, 30.9, 19.2, 14.5. (3Z, 3’Z)-4, 4’-(Propane-1, 3-diylbis(azanediyl))dipent3-en-2-one (5b) Solid, mp: 43-45 oC (Lit.10 50-52 oC); IR (KBr) nmax/cm-1: 3442, 2940, 1606, 1438, 1363, 1294, 1123, 1016, 742; 1H NMR (300MHz, CDCl3): d 10.87 (br s, 1H, NH), 4.98 (s,

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1H), 3.32-3.38 (m, 2H), 1.99 (s, 3H), 1.92 (s, 3H), 1.851.89 (m, 1H); 13C MNR (75MHz, CDCl3): d 195.2, 163.2 95.6, 39.6, 30.2, 28.8, 18.8. (2Z,2’Z)-Diethyl 3,3'-(1,4-phenylenebis(azanediyl))dibut2-enoate (5c)27 Solid, mp: 135-137 oC (Lit.11 135 oC); IR (KBr) nmax/ -1 cm : 2450, 2979, 2929, 1617, 1484, 1385, 1256, 1056, 780, 679; 1H NMR (300MHz, CDCl3): d 10.34 (br s, 2H, NH), 7.04 (s, 4H), 4.70 (s, 2H), 4.15 (q, J 7.2Hz, 4H), 2.00 (s, 6H), 1.29 (d, J 7.2Hz, 6H); 13C MNR (75MHz, CDCl3): d 170.3, 158.7, 136.2, 124.9, 86.2, 58.7, 20.2, 14.5.

(Z)-4-(2-Aminophenylamino)pent-3-en-2-one (6b) Solid, mp: 129-131 oC (Lit.6 not reported); IR (KBr) nmax/cm-1: 3759, 3445, 2931, 1624, 1426, 1256, 1255, 1114, 765; 1H NMR (300MHz, CDCl3): d 12.47 (br s, 1H, NH), 6.98-7.28 (m, 4H), 5.21 (s, 1H), 2.10 (s, 3H), 2.02 (s, 3H); 13 C MNR (75MHz, CDCl3): d 196.7, 159.3, 140.1, 134.6, 130.1, 125.4, 124.5, 122.6, 98.4, 29.3, 19.9.

References 1. Zhang, Z. H.; Yin, L.; Wang, Y. M.; Adv. Synth. Catal. 2006, 348, 184. 2. Khodaei, M. M.; Khosropour, A. R.; Kookhazadeh, M.; Synlett

(3Z,3’Z)-4,4’-(1,4-Phenylenebis(azanediyl))dipent-3-en2-one (5d)28 Solid, mp: 185-187 oC (Lit.12 172 oC); IR (KBr) nmax/ -1 cm : 3442, 2926, 1614, 1568, 1492, 1430, 1267, 1177, 1008, 865, 737; 1H NMR (300MHz, CDCl3): d 11.96 (br s, 2H, NH), 7.07 (s, 4H), 5.19 (s, 2H), 2.10 (s, 6H), 2.00 (s, 6H); 13C MNR (75MHz, CDCl3): d 196.3, 159.8, 136.1, 125.1, 97.8, 29.1, 19.8.

2004, 1980. 3. Xu, F.; Lv, H.-X.; Wang, J.-P.; Tian, Y.-P.; Wang, J.-J.; J. Chem. Res. 2008, 707. 4. Roberts, E.; Turnur, E. E.; J. Chem. Soc. 1927, 1832. 5. Chen, X.; She, J.; Shang, Z. C.; Wu, J.; Wu, H. F.; Zhang, P. Z.; Synthesis 2008, 3478. 6. Song, Z. Y.; Bai, D. R.; Yu, H. T.; Xu, L. L.; Zhang, W. X.; Meng, J. B.; Matsuura, T.; Chin. Chem. Lett. 2004, 15, 127. 7. Jacobs, J.; Kesteleyn, B.; De Kimpe, N.; Tetrahedron 2008, 64,

(Z)-Ethyl 3-(2-aminophenylamino)but-2-enoate (6a)29 Solid, mp: 77-79 oC (Lit.13 85 oC); IR (KBr) nmax/cm-1: 3408, 3285, 2965, 1609, 1448, 1270, 1159, 1065, 784, 695; 1H NMR (300MHz, CDCl3): d 9.70 (br s, 1H, NH), 7.04-7.10 (m, 2H), 6.68-6.76 (m, 2H), 4.72 (s, 1H), 4.15 (q, J 7.2Hz, 2H), 3.84 (br s, 2H, NH), 1.80 (s, 3H), 1.28 (t, J 7.2Hz, 3H); 13C MNR (75MHz, CDCl3): d 170.6, 161.5, 143.5, 128.6, 128.0, 124.7, 118.3, 115.6, 85.1, 58.7, 19.7, 14.6.

7545. 8. Zhang, Y.; Raines, A. J.; Flowers, R. A.; J. Org. Chem. 2004, 69, 6267. 9. Vohra, R. K.; Renaud, J. L.; Bruneau, C.; Synthesis 2007, 731. 10. Zhang, Z. H.; Hu, J.-Y; J. Braz. Chem. Soc. 2006, 17, 1447. 11. Bangdiwala, B. P.; Desai, C. M.; J. Indian Chem. Soc. 1954, 31, 688. 12. Kudryavtsev, A. S.; Savich, I. A.; Khimiya 1962, 17, 57. 13. Sexton, W. A.; J. Chem. Soc. 1942, 303.

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Figure S1. 1H NMR of 3a (300 MHz, CDCl3) and 13C NMR of 3a (75 MHz, CDCl3).

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Figure S2. 1H NMR of 3b (300 MHz, CDCl3) and 13C NMR of 3b (75 MHz, CDCl3).

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Figure S3. 1H NMR of 3c (300 MHz, CDCl3) and 13C NMR of 3c (75 MHz, CDCl3).

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Figure S4. 1H NMR of 3d (300 MHz, CDCl3) and 13C NMR of 3d (75 MHz, CDCl3).

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Figure S5. 1H NMR of 3e (300 MHz, CDCl3) and 13C NMR of 3e (75 MHz, CDCl3).

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Figure S6. 1H NMR of 3f (300 MHz, CDCl3) and 13C NMR of 3f (75 MHz, CDCl3).

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Figure S7. 1H NMR of 3g (300 MHz, CDCl3) and 13C NMR of 3g (75 MHz, CDCl3).

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Figure S8. 1H NMR of 3h (300 MHz, CDCl3) and 13C NMR of 3h (75 MHz, CDCl3).

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Figure S9. 1H NMR of 3i (300 MHz, CDCl3) and 13C NMR of 3i (75 MHz, CDCl3).

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Figure S10. 1H NMR of 3j (300 MHz, CDCl3) and 13C NMR of 3j (75 MHz, CDCl3).

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Figure S11. 1H NMR of 3k (300 MHz, CDCl3) and 13C NMR of 3k (75 MHz, CDCl3).

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Figure S12. 1H NMR of 3l (300 MHz, CDCl3) and 13C NMR of 3l (75 MHz, CDCl3).

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Figure S13. 1H NMR of 3m (300 MHz, CDCl3) and 13C NMR of 3m (75 MHz, CDCl3).

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Figure S14. 1H NMR of 3n (300 MHz, CDCl3) and 13C NMR of 3n (75 MHz, CDCl3).

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Figure S15. 1H NMR of 3o (300 MHz, CDCl3) and 13C NMR of 3o (75 MHz, CDCl3).

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Figure S16. 1H NMR of 3p (300 MHz, CDCl3) and 13C NMR of 3p (75 MHz, CDCl3).

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Figure S17. 1H NMR of 3q (300 MHz, CDCl3) and 13C NMR of 3q (75 MHz, CDCl3).

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Figure S18. 1H NMR of 3r (300 MHz, CDCl3) and 13C NMR of 3r (75 MHz, CDCl3).

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Figure S19. 1H NMR of 3s (300 MHz, CDCl3) and 13C NMR of 3s (75 MHz, CDCl3).

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Figure S22. 1H NMR of 5c (300 MHz, CDCl3) and 13C NMR of 5c (75 MHz, CDCl3).

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Figure S23. 1H NMR of 5d (300 MHz, CDCl3) and 13C NMR of 5d (75 MHz, CDCl3).

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